Side Effects and Contraindications of Bisoprolol

Bisoprolol is one of the most widely used cardioselective beta-blockers: it is prescribed for arterial hypertension, coronary heart disease and chronic heart failure. The drug is well studied and generally well tolerated, but it has a predictable set of adverse effects and clear contraindications. The editorial team examined exactly what can go wrong, for whom bisoprolol is not suitable, and why people who train should know more about it than the average patient.

Where side effects come from

Bisoprolol blocks beta-1 adrenergic receptors, which are located mainly in the heart and kidneys. When adrenaline and noradrenaline cannot fully act on these receptors, the heart contracts less often and with less force, renin release decreases, and with it arterial pressure. This is the basis of the drug's therapeutic action, and it is also the source of most of its adverse effects.

In other words, most of bisoprolol's side reactions are a «continuation» of its main pharmacology. Excessive slowing of the pulse, a drop in pressure, a feeling of fatigue on exertion are direct consequences of the heart responding less to sympathetic stimulation. This is important to understand: such effects often depend on the dose and the speed of its increase.

Bisoprolol's cardioselectivity is one of the highest among beta-blockers, meaning the drug acts much more strongly on beta-1 receptors than on beta-2, which are responsible for dilating the bronchi and the vessels of skeletal muscles. However, selectivity is relative: it gradually weakens as the dose increases. So the risk of bronchospasm or cold extremities is not zero even for the «most selective» drug.

Another part of the side effects is related to the central nervous system: sleep disturbances, vivid dreams, dizziness. Bisoprolol is moderately lipophilic and partly crosses the blood-brain barrier, although such complaints occur less often than with highly lipophilic drugs like propranolol.

Finally, some reactions appear at the start of treatment or after a dose increase and weaken over time. That is why in chronic heart failure doctors start with minimal doses and slowly titrate the drug, monitoring well-being, pulse and pressure at each step.

The most common adverse reactions

In the drug's prescribing information the frequency of side effects is divided into categories: «very common» (more than 1 in 10 patients), «common» (1 to 10 in 100), «uncommon» (1 to 10 in 1000) and rarer. For patients with heart failure receiving bisoprolol, bradycardia falls into the «very common» category, and worsening of heart failure symptoms during titration falls into «common».

Among people with hypertension or angina, the most common complaints are fatigue, dizziness and headache, especially in the first weeks. Sensations of cold or numbness in the fingers and toes often appear, as well as gastrointestinal disorders: nausea, diarrhea or constipation.

A drop in pressure, in particular orthostatic hypotension (dizziness on standing up abruptly), is also among the typical effects. It occurs more often in older people and in those who simultaneously take other antihypertensive agents or diuretics.

Sexual function deserves separate mention. A decrease in potency is noted in the prescribing information as a rare reaction. At the same time, studies with beta-blockers have shown a significant contribution of the nocebo effect: patients who were told about such a possible effect complained of it noticeably more often. So it is better not to stay silent about the problem but to discuss it with a doctor.

Rare and serious complications

The most serious risks of bisoprolol are related to the heart's conduction system. In people with existing disorders — sick sinus syndrome, atrioventricular block — the drug can deepen conduction disturbances up to dangerous pauses in the heart's work. That is precisely why an ECG is mandatory before prescribing.

The second category is decompensation of heart failure. Although in the long term bisoprolol reduces mortality in heart failure with reduced ejection fraction, during rapid dose escalation fluid retention, shortness of breath and edema may increase. Monitoring body weight and symptoms during titration is standard practice.

The third important risk is withdrawal syndrome. Abruptly stopping the drug after prolonged treatment can cause a rebound increase in pulse, a rise in pressure, and in patients with coronary heart disease an exacerbation of angina and even a heart attack. Guidelines and the prescribing information recommend reducing the dose gradually, under a doctor's supervision.

Rare reactions also include allergic rashes, itching, exacerbation of psoriasis, elevated liver enzymes, hearing disturbances, dry eyes (important for those who wear contact lenses) and changes in the lipid profile, in particular increased triglycerides.

In people with diabetes mellitus, bisoprolol can mask the signs of hypoglycemia, primarily tachycardia and tremor. Sweating in this case usually persists. This is not a reason to avoid the drug, but a reason to monitor glucose more often, especially on insulin or sulfonylurea drugs.

Contraindications and precautions

The prescribing information for bisoprolol contains a list of absolute contraindications in which the drug must not be prescribed. Most of them concern the state of the heart and bronchi, as well as situations in which the body is critically dependent on sympathetic stimulation.

• acute heart failure or decompensation requiring intravenous inotropic agents;
• cardiogenic shock;
• second- to third-degree atrioventricular block without a pacemaker, sinoatrial block, sick sinus syndrome;
• symptomatic bradycardia and symptomatic hypotension;
• severe bronchial asthma;
• severe forms of occlusive peripheral artery disease and Raynaud's syndrome;
• untreated pheochromocytoma;
• metabolic acidosis;
• hypersensitivity to bisoprolol or excipients.

In addition, there are a number of conditions in which the drug is used with caution: diabetes mellitus with glucose fluctuations, strict fasting, chronic obstructive pulmonary disease, first-degree AV block, Prinzmetal's angina, psoriasis, desensitizing therapy with allergens. Beta-blockers can increase the severity of anaphylactic reactions and reduce the response to adrenaline.

Before elective surgery under general anesthesia, the anesthesiologist must know that the person is taking bisoprolol. The drug is usually not discontinued, since withdrawal is more dangerous, but accounting for its action helps avoid excessive bradycardia and hypotension.

As for pregnancy, beta-blockers can reduce placental blood flow and affect fetal growth, and in a newborn they can cause bradycardia and hypoglycemia. The decision to take the drug during pregnancy or breastfeeding is made only by a doctor after weighing the benefit-risk ratio. In thyrotoxicosis bisoprolol can conceal symptoms, which complicates assessment of the condition.

Bisoprolol and physical exertion

For people who train, the main peculiarity of bisoprolol is the limitation of the maximum heart rate. Pulse zones calculated by formulas for healthy people lose their meaning while taking the drug: a person may feel severe fatigue while the heart rate monitor shows a «light» zone.

In such cases cardiologists advise relying on a subjective exertion scale (the Borg scale) or on pulse zones determined during a stress test performed while already on treatment. This is safer and more accurate than any calculations.

It is also worth remembering that beta-blockers are on the WADA Prohibited List (section P1), but only for certain sports where precision and control of tremor matter: archery, shooting, golf, darts, billiards, motorsport and some other disciplines. Athletes in these sports need a therapeutic use exemption (TUE) for treatment.

If, however, a person does fitness for health, bisoprolol is not an obstacle to training. On the contrary, regular moderate activity is part of the treatment of hypertension and heart failure. It is only important to agree the level of exertion with a doctor and not to combine the drug with stimulants without consultation.

Editorial conclusions

Most of bisoprolol's side effects — bradycardia, fatigue, cold extremities, dizziness — follow directly from its mechanism of action and often depend on the dose and the pace of its increase.

The most dangerous risks concern people with cardiac conduction disorders, decompensated heart failure and severe asthma, as well as situations of abrupt withdrawal of the drug.

For those who train, bisoprolol changes the pulse response to exertion, so intensity should be controlled by how you feel and by the results of a stress test, rather than by standard formulas.

We also recommend reading our materials «Interaction of bisoprolol with other drugs», «Tests while taking bisoprolol» and «Nebivolol or bisoprolol: what is the difference».

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